Method for preparing sulfur-containing carboxylic acids



Patented July 8, 1952 UNITED STATES PATENT OFFICE ration of New York 1%Drawing. Application June 18, 1947, Serial'No. 755,477

4 Claims. (01. at -at) This invention relates to a method for thepreparation of sulfur=contaiiiin carbbiiyli'c acids, and pertains morespecificauy to" the preparation of such compounds by the reaction of achlorinated hydrocarbon with a mercapto-substituted aliphaticc-arboxylic acid.

With halogenated hydrocarbons the order of activity decreases inpassing' from the iodide to the fluoride, from tertiary to primarycompounds, and from compounds containing one carbon atom to compoundscontaining two or more carbon atoms. Consequently, chlorinatedhydrocarbons, and especially the primary compounds containin two or morecarbon" atoms, show unusual stability and lircliriarilyundergo lnetathtica-l reactions withother organic compounds veryslowly'ornot atall. As a resulti-t is generally necessary to" employ a bromine oriodine-containing compound eral-lyfroriil toe-,read ily react'swithamer'c'apto-f acid of the formula HS'R COOH-, wherein R is abivalent aliphatic hydrccarbeii radical; in an aqueous medium thepresence-of an" alkali metal. hydroxide, suchas NaOH and KOH, to formanalkall-nietal salt o'f asulf-ur-con'tain iiig carbox-ylic acid-fromwhich, on addition ofa strong mineral acid, such as HCl and H2304, thereis obtained a free suirumontainmg' car' boxylic acid of the generalformula:

lvgs-iz-r -onh wherein A, R", and a; have the same meaning set forthabove; I V

'The ease" with which such chlorinated'hydi'o carbons and suchmercapto-acids may be reacted, according tothis invention, makes thisreaction a: veryvaiuame one for the production of Various sulrurcontammg monoand pmy-cai-tox'yiic' acids, which are extremely useful--organic compounds} The acids and their water-soluble salts are useful asplant growth stimulants andas' inhibitors O'f' rancidity'in edibleanimal and vegetable oils"; and esters of the acids are excellent 2plasticizers for synthetic resins such as polyvinyl lo i It is desirablethat i a hl lri eiedhi n c mme white. ases gi iiha xeeet 9 s r iq 'ifsiniaie l s t an 112 'atb j a. and nr a lyie er th n ...H ver poundscontaining more than "12 carbon atoms mayalso be used,

The preferred pounds which are used in the reaction are comi poundswhich possess the formula Cl-A-Cl, 77115179111 A E3: .hyd r enradi awhich may either be 'sjtraight 0hairi or branched and which may have itsconnecting: valences on the same or different carbon atoms. Includedamong these compoun are, dichloroinethane; 1,2-dich1oroethane;1",3-dichlorop'ropane}; lifl-jdichlorobutane, 1,1-dichloropropane,1,2'-dichloropropane, 2,2-dichloropropane, l, l-d ichloroetha ne',' 1,-3di-chloro 2 riiet-h'yIbutanQ-ZB; dichloro 2-methy1butane, and othersimilar dichlorinated hydrocarbons which may be prepared byhalogena-tingparent-hydrocarbons including-pentanes',

hexanes, heptanes, octane'si' deems-and dodecanes.

Qther chlorinated hydrocarbons which are used include" 'allg'y-lchloridesiisllch a'sj cmor gnetnane; l-chloropropane, Z-chloropropang,1-ch1oIoE2} dimethyl propane, 2-chloro-2-methy1 propane,

methyl but'ane 1 chloro 3f rnethyl-butarie} 2- chloro 2 methylbutane, 1chlorispentaneg-a chloropent'ane, 3 chloropentane, i chloro-f hexane, 2chloro hekanqi I hlo'rohe'ptanei' 1 chloro-octane, 2 ohmic-octane,is'op'ro'pyl chloride, isobutyl chloride, and the like;

Unsaturated chlorinated hydrocarbon com 'i Tri-chlorinated" hydrocarbonssuch as" tri chloromethane, 1,1,2-tri-chloroethane,1,1,1-trichloroethane, 1,2,3-tri-ch1orobutane, and the like;

Tetra-chlorinated hydrocarbons, such as car bon tetrachloride,1,1,2,2-tetra-ch1oroethane and' the like;

Chlorinated aralkyl hydrocarbons such as benzyl chloride, benzalchloride and th'elikef Chlorinated alicyclic hydrocarbons in which thechlorine is attached to saturated carbon atoms such aschlorocyclohexane, 1,2-dichlorocyclohexane and the like.

Thus it can be seen that the invention is ap- 5 plicable to allchlorinated hydrocarbons in which the chlorine atoms are attached onlyto saturated carbon atoms. A saturated carbon atom is one which isconnected to four different atoms by single valences, as distinguishedfrom carbon atoms having an unsaturated linkage (i. e., two or threevalences), connected to a single atom.

The mercapto-acids which are used in the re-, action of this inventionpossess the formula l-thia-B-phenyl-pcntanoic acid CHClz4,7-ditl1la-5,6-(di-Z-carboxyethylthio)-decanedioic acid (tetrakis(Z-carboxyethylthio) ethane) The reaction or" this invention is bestcarried out in the presence of a water solution containing sufficientdissolved alkali to neutralize all of the acid present or formed in thereaction. Preferably, the mercapto-acid is added to the wateralkalisolution in a cooling bath. After the addition is complete, the coolingbath is removed and the chlorinated hydrocarbon compound is added to themixture, and this reaction mixture is refluxed at a temperature at ornear the refluxing temperature of water. Accordingly, temperatures inthe range of from C. to C. are preferred, but temperatures as low as 25C. and as high as C. may be used with good results. The reaction takesplace rapidly and is complete in most cases in from thirty minutes totwo hours. The reaction mixture is then allowed to cool to roomtemperature and hydrochloric acid is added. A precipitate forms which isfiltered, dried, and purified by recrystallizing from an organic solventto produce the pure sulfur-containing acid.

The following specific examples illustrate the reaction of thisinvention, but are not intended to limit the invention, for there are,of course, numerousv modifications. In the examples all parts are byweight.

Example I 164 parts (4.05 moles) of sodium hydroxide are dissolved in1500 parts or water maintained in a cooling bath. 218 parts (2.05 moles)of betamercaptopropionic acid are then added slowly and with constantstirring. The cooling bath is then removed and 99 parts (1.0 mole) of1,2dichloroethane added. The mixture is then heated at a temperature of96-104 C. for a period of 45 minutes. 500 parts of dilute hydrochloricacid are then added and the precipitate which forms is filtered, washedwith hexane, and dried for forty-eight hours at 75 C. 230 parts (96.7%conversion based on the ethylene dichloride) of 4,7-

dithia-idecanedioic acid. (M. P. 156-160 C.) are formed.

Example II 164 parts (4.1 moles) of sodium hydroxide are dissolved in1000 parts of water maintained in cooling bath. 189 parts (2.05 moles)of mercaptoacetic acid are then added slowly and with-constant stirring.The cooling bath is then removed and 99 parts (1.0 mole) of1,2-dichloroethane added. The mixture is then heated at a temperature of105 C. for a period of 90 minutes. After the mixture cools, 175 parts ofconcentrated hydrochloric acid are added, and a precipitateslowly'forms. The precipitate is filtered and recrys tallized from methylethyl ketone, .andthe filtrate is extracted with ether. After theetheris rcmoved the residue solidifies. A total of 189.5 parts (90.2%)of 3,6-dithia-octanedioic acid (M. P. 105.5 C.-108.5 C.) are formed.

Calculated for CeHioOiSz:

Per cent H -1 4.77

Per cent C 34.22

Percent S 30.45 Neutralization equivalent -1 105.06

Found for 0611100482: 7

Per cent H 4.76

Per cent C 34.29

Percent S 30.43 Neutralization equivalent 105 Example III 164 parts (4.1moles) of sodium'hydroxide are dissolved in 1500 parts of watermaintained in a cooling bath. 218 parts (2.05 moles) ofbeta-mercaptopropionic acid are then added with constant stirring. Ifdesired, nitrogen gas is continuously bubbled through the reactionmixture to prevent the oxidation of the beta-mercaptopropionic acid andthereby enhance the yield of the desired product. The cooling bath isthen removed and 113 parts (1 mole) of trimethylene dichloride added.The reaction mixture is then heated to a temperature of 103 C. for aperiod of 55 minutes. After adding 500 parts of water, 500 parts ofdilute hydrochloric acid are-added. A precipitate of 202 parts (80.3%)of 4,8-dithiaundecanedioic acid (M. P. 109.5 C.-111.5 C.) is formed.

Calculated for C9H16O4S2;

Per cent H 6.40 Percent C 42.85 Per cent S 25.38 Neutralizationequivalent 126 Found for C9H16O4S2:

Per cent H 6.41 Per cent C 42.83 Per cent S 25.40 Neutralizationequivalent 127 Example IV 246 parts (6.15 moles) of sodium hydroxide aredissolved in 1500 parts of water maintained in a cooling bath. 283 parts(3.075 moles) of mercaptoacetic acid are then added with constantstirring. The cooling bath is removed and 170 parts (1.5 moles) oftrimethylene chloride added. The reaction mixture is then heated to atemperature of 98 C. to 102 C. for a period of 10 minutes. 690 parts ofconcentrated hydrochloric acid are added after the mixture cools toabout 50- C. 295 parts (87.8%) of 3,7-dithia-nonanedioic acid areformed.

6. Calculated for C7H1204S2I Per cent .11 421-141..-- 5.35 Per cent .0"37.54 Neutralization. equivalent 112 Found for C'IH12O4S2Z Per cent H5.38' Per cent C 1....-- 37.55 Neutralization equivalent -1 112 ExampleV 208 parts (5.2 moles) of sodium hydroxidefiare.

Calculated for CibH14O4S2:

Per cent I-I 6.77 Per cent C 45.1 Per cent S 24.05 Neutralizationequivalent "133 Found for 010151140452! Per cent H 6180 Percent 'C 4507Percent S 24.02 Neutralization equivalent 133 Example VI 216 parts (5.4moles) of sodium hydroxide are dissolved in 1200 parts of watermaintained in a cooling bath. 159 parts (1.25 moles) of1,4-dichlorobu'tane are dissolved in 248 parts (2.7 moles)ofmercapto'acetic acid and 395 parts of ethyl alcohol and this mixtureis added rapidly to the sodium hydroxide-water mixture. There'- actionmixture is'thenheated'at a temperature of 78 to 80 C. for a period ofminutes. After cooling to a temperature of 65 C., 542 parts ofconcentrated hydrochloric acid are added. At this point two layers formand the lower layer is drawn off and washed successively with benzene,ethyl alcohol, and ethyl ether. 151 parts (51.1%) of3,8-dithia-decanedioic acid are formed.

Example VII 120 parts (3 moles) of sodium hydroxide are dissolved in1200 parts of water maintained in a cooling bath. 159 parts (1.5 moles)of betamercapto-propionic acid are then added very slowly and withconstant stirring. 190 parts (1.5 moles) of benzyl chloride are thenadded and the cooling bath is removed. The reaction mixture is heated toa temperature of 104 C. for a period of minutes after which the mixtureis allowed to cool to room temperature. 230 parts of concentratedhydrochloric acid are then added and the mixture is cooled in an icebath. A lower layer is formed which solidified on cooling. Thesolidified material is then filtered and washed with benzene. It is thenrecrystallized from benzene and 279 parts (94.9%) of 4-thia-5- phenylpentanoic acid are formed.

Although specific examples have been herein described, it is notintended to limit the invention thereto, for numerous variations inproportions and reaction conditions will be apparent to those skilled inthe art and are within the spirit and scope of the appended claims.

We claim:

1. A method of preparing a compound of the formula wherein A is asaturated aliphatic hydrocarbon radical having its connecting valenceson saturated carbon atoms, R is alkylene, and a: is a number equal tothe valence of A, which comprises reacting a mercapto-acid of theformula HS-RCOH wherein Ris alkylene, with a compound of the formulaA(Cl)1, wherein A is a saturated aliphatic hydrocarbon radical havingits connecting valences on saturated carbon atoms, and a: is a numberequal to the valence of A, in an aqueous medium in the presence of analkali metal hydroxide, and then acidifying the reaction mixture.

2. A method of preparing a compound of the formula A(SR-COH)= wherein Ais a saturated aliphatic hydrocarbon radical of less than 8 carbon atomshaving its connecting valences on saturated carbon atoms, R is alkylene,and m is a number equal to the valence of A, which comprises reacting amercapto-acid of the formula HSRCl-OH wherein R is alkylene, with acompound of the formula A(Cl)', wherein A is a saturated a1iphatichydrocarbon radical of less than 8 carbon atoms having its connectingvalences on saturated carbon atoms, and a: is a number equal to thevalence of A, in an aqueous medium in the presence of an alkali metalhydroxide, and then acidifying the reaction mixture.

3. A method of preparing a compound of the formula wherein R is alkyleneand A is a saturated aliphatic hydrocarbon radical of less than 8 carbonatoms having its connecting valences on saturated carbon atoms, whichcomprises reacting a mercapto-acid of the formula wherein R is alkylene,with a compound of the formula ClACl wherein A is a saturated aliphatichydrocarbon radical of less than 8 carbon atoms having its connectingvalences on saturated carbon atoms, in the presence of an aqueoussolution of an alkali metal hydroxide, and then acidifying the reactionmixture.

4. A method of preparing 4,7-dithia-decandioic acid of the formula H0I%CH;CH;SCH -CH SCHzCHgfi-0H which comprises reactingbeta-mercaptopropionic acid with 1,2-dichloroethane in the presence ofan aqueous solution of an alkali metal hydroxide, and then acidifyingthe reaction mixture.

JAMES 'I. GREGORY. JACOB E. JANSEN.

REFERENCES CITED The following references are of record in the file ofthis patent:

Beilstein: Organische Chemie, vol. 6, 4th ed., p. 463 (1923).

Welde: Journ. Prak. Chem. (2), vol. 15, p. 52 (1877).

Suter et al.: Beilstein, Handbuch der Org. Chem. (4th ed.), vol. 6, p.463 (1923).

Benary: Beilstein, Handbuch der Org. Chem. (4th ed.), vol. 3, sup., p.(1929).

Rothstein et al.: Beilstein, Handbuch der Org. Chem. (4th ed.) v01. 3,2nd sup., p. 176 (1942).

1. A METHOD OF PREPARING A COMPOUND OF THE FORMULA